Monocytes when activated may have a role in host defense against tumors. Some biochemical mechanisms associated with activation of monocytes have been investigated. The effects of agents, such as interferon (IFN), the chemotactic peptide N-formyl-L-methionyl-L-phenylalanine (FMLP) and the tumor promoter 12-tetradecanoyl phorbol 13-acetate (TPA), have been examined. Methylation reactions are required for the expression of several cellular activities. Of these different methylation reactions, phospholipid (PL) methylation is of considerable interest for its role in modifying the physical state of cellular membranes. We have shown that IFN induced an inhibition on PL methylation by mononuclear cells, an effect that might contribute to alterations in the properties of the membrane of IF treated cells. We have demonstrated and characterized the presence of a methylated nonpolar lipid fraction in monocytes, lymphocytes and a variety of tumor cell lines. Ubiquinone-50 was identified as the major methylated nonpolar lipids and the regulation of its biosynthesis via methionine-dependent reactions by monocytes was defined. An inverse relationship between activation of the oxidative burst and the rate of phospholipid and nonpolar lipid methylation was observed. Both methylation reactions were similarly affected, suggesting a common mechanism of regulation. Oxidation of methionine to methionine sulfoxide by stimulated monocytes was observed which led to the possibility, currently under investigation, that this phenomenon might limit the availability of intracellular methyl donors. The inhibitory effects on lipid methylations observed in stimulated monocytes contributes to our understanding of the mechanisms of regulation of methylation reactions in these cells and suggest a relevant role of these pathways in the response of monocytes to stimulants.